Feline immunodeficiency virus (FIV) is a feline analog of human immunodeficiency virus (HIV). Transmucosal infection by FIV in cats could serve as a useful model for mucosal HIV transmission; early stages in transmucosal infection and immune responses can be examined and used to evaluate the efficacy of mucosal immunization strategies. Aim 1 of this proposal will compare the transmission efficiency of transmucosal cell- free versus cell-associated FIV, as assessed by virus isolation, polymerase chain reaction (PCR), antibody response, and virus specific lymphocyte proliferation. [Preliminary data demonstrates that cell- associated virus is transmitted transmucosally more efficiently and can result in decreased CD4 counts, decreased lymphocyte proliferation to Con A, and clinical signs. Therefore, the model is viable to study the early immune changes seen in transmucosal lentivirus infection.] Aim 2 will identify the nature and magnitude of the virus-specific humoral and cell- mediated immune responses following mucosal (vs. parenteral) infection. Virus-specific lymphocyte proliferation and cytotoxic lymphocyte activity will be compared in mucosal and systemic lymphoid tissues. Humoral response will be evaluated by total and virus specific serum and secretory immunoglobulin concentration. Aim 3 will evaluate the efficacy of mucosal, parenteral, and combination vaccination strategies employing polymer- encapsulated whole formalin-inactivated FIV to induce mucosal immunity. Mucosal, regional lymph node, and systemic immune responses and virus burden will be evaluated following immunization and mucosal challenge. An overall goal of this work will be to determine whether indicators of systemic immune function adequately represent mucosal immune function in lentivirus infection.